NEW DRUGS FOR OPPORTUNISTIC INFECTIOUS DISEASES

治疗机会性传染病的新药

• 批准号: 3141179
• 负责人: ALICE M. CLARK
• 金额: $ 14.21万
• 依托单位: UNIVERSITY OF MISSISSIPPI
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-07-01 至 1995-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3141179
• 关键词: Candida albicans; Cryptococcus neoformans; Mycobacterium intracellulare; antibacterial agents; antifungal agents; disease /disorder model; drug adverse effect; drug design /synthesis /production; laboratory mouse; microorganism disease chemotherapy; nonhuman therapy evaluation; opportunistic infections; plant extracts; tissue /cell culture

Acquired Immunodeficiency Syndrome (AIDS) is characterized by a breakdown in the immune system which is manifested in the form of serious opportunistic infections. Treatment of such infections is often inadequate for a variety of reasons, including the lack of effective antimicrobial therapy. The most common AIDS-related fungal and bacterial opportunistic infections are cryptococcosis, candidiasis, histoplasmosis, and mycobacteriosis. Historically, most bacterial infections and localized fungal infections have been effectively treated with one of the numerous clinically available antibiotics. However, the need for new, more effective and less toxic antibiotics for the treatment of disseminated fungal and mycobacterial infections is obvious in light of the significant toxicities and failure rates of the currently available agents. The discovery of new antibiotics has in the past successfully relied primarily upon the isolation of such agents from natural sources. The major advantage of this approach over chemical synthesis or modification of existing agents is the likelihood of identifying new prototype drugs with quite different chemical structures, and hence, less likelihood of similar toxicities, cross-resistance, and mechanisms of action. Although microorganisms have traditionally served as the primary source of new antibiotics, it has recently been shown that higher plants also serve as sources for a number of diverse and novel antimicrobial agents. The objective of this project is to discover new prototype antibiotics with potential utility specifically for the treatment of AIDS-related opportunistic disseminated mycoses and mycobacteriosis. This goal will be accomplished by the initial in vitro evaluation of antifungal and antimycobacterial activity of extracts of higher plants. Plant extracts which show good activity will be fractionated and purified using a bioassay-directed scheme. This approach ensures that relatively little time and effort will be wasted in isolating inactive materials. Pure active compounds with significant minimum inhibitory concentrations (MIC) will be evaluated for in vivo efficacy in established animal models of disseminated mycosis and mycobacteriosis in order to determine their potential clinical utility.

获得性免疫缺陷综合症（艾滋病）的特点是身体崩溃 在免疫系统中，表现为严重的形式 机会性感染。 此类感染的治疗通常是 由于各种原因，其中包括缺乏有效的 抗菌治疗。 最常见的与艾滋病相关的真菌和细菌 机会性感染有隐球菌病、念珠菌病、组织胞浆菌病、 和分枝杆菌病。 从历史上看，大多数细菌感染和局部真菌感染 已通过众多临床治疗方法之一得到有效治疗 可用抗生素。 然而，需要新的、更有效的和 毒性较小的抗生素，用于治疗播散性真菌和 鉴于显着性，分枝杆菌感染是显而易见的 目前可用药剂的毒性和失败率。 这 过去，新抗生素的发现成功依赖于 主要是从天然来源中分离出此类物质。 这 这种方法相对于化学合成或修饰的主要优点 现有药物的可能性是识别新原型药物的可能性 具有完全不同的化学结构，因此不太可能 相似的毒性、交叉耐药性和作用机制。 虽然 传统上微生物是新物质的主要来源 最近发现高等植物也可作为抗生素 许多不同的新型抗菌剂的来源。 该项目的目标是发现新的抗生素原型 具有专门用于治疗艾滋病相关疾病的潜在用途 机会性播散性真菌病和分枝杆菌病。 这个目标将 通过抗真菌药物的初步体外评估来完成 高等植物提取物的抗分枝杆菌活性。 植物提取物 表现出良好活性的物质将使用 生物测定指导计划。 这种方法确保相对较少 时间和精力将浪费在隔离非活性材料上。 纯的 具有显着最低抑制浓度 (MIC) 的活性化合物 将在已建立的动物模型中评估体内功效 播散性真菌病和分枝杆菌病，以确定其 潜在的临床实用性。